Diseases of the circulatory system are a major cause of illness in animals, especially humans, and are responsible for many deaths. In such diseases, decreased tissue oxygenation or ischemia is present. Such decreased tissue oxygenation may be due to a variety of causes. For example, decreased cardiac output can result in decreased perfusion, as can vasoconstriction, partial or complete blockage of blood vessels, leaking or burst blood vessels, decreased oxygenation of the perfusate (as a result of anemia or abnormal hemoglobin), and decreased ability of tissue to extract oxygen. One such disease is atherosclerosis, which is characterized by fatty deposits on the inner surfaces of arteries, which inner surfaces are lined with endothelial cells. These deposits narrow the arteries, resulting in reduced blood flow in such areas of constriction and cause the heart to work harder to drive blood through the circulatory system. In turn, this may lead to a rise in blood pressure. As the blood pressure rises, so does the risk that a blood vessel having a weakness in the wall may rupture, resulting in an aneurism. Other risks relate to the roughness of the artery walls, which may cause blood to clot, thereby causing a blockage where such a clot blocks an arteriole. Or, a piece of the roughened and irregular artery wall may break off and be carried by the blood flow until it reaches an arteriole so narrow that it cannot pass through and thus totally occludes it. If a blockage occurs in the heart, a myocardial infarction or heart attack results. If it occurs in the brain, a stroke results.
In another serious condition, narrowing of coronary arteries due to atherosclerosis may lead to angina or chest pain upon exertion. When the coronary arteries narrow, less blood reaches the heart, and it cannot continue to pump because it needs more oxygen than the narrowed coronary arteries provide. It is this disparity between oxygen supply and demand that results in chest pain (angina) and, possibly, heart attack. Coronary arteries also contract and restrict blood flow in response to a variety of stimuli, one such stimulus being adrenaline or epinephrine, which is released in response to stress. As is well known, when a person faces a stressful situation, adrenaline is released from the adrenal glands and flows into the blood stream and then to the heart. The coronary arteries contract and even less oxygen becomes available to the heart. This may account for those situations which have been reported anecdotally in which people suffer heart attacks when faced with shock or tragic news.
In conditions such as these which result from decreased tissue oxygenation (anoxia, which is defined as the absence or lack of oxygen and is hereafter generically employed to include hypoxia, which is defined as the deficiency or shortage of oxygen), it has been found that such anoxia induces a spasm or contraction in the blood vessels (vasospasm) supplying the anoxic tissue. These spasms have the effect of further reducing the blood supply to the tissue in question thereby further aggravating the effects of the lack of tissue oxygenation. Frequently, this results in irreversible damage to certain tissue, such as heart tissue, which cannot be revived after its death. This process of secondary vasospasm, or further contraction of the arteries and even further restriction of blood flow, is mediated by the endothelium, which releases a material that has been identified as Endothelium-Derived Contracting Factor or EDCF.